自噬:细胞死亡的调控者。
Autophagy: Regulator of cell death.
机构信息
School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China.
The Second School of Clinical Medicine, Xinjiang Medical University, Urumqi, China.
出版信息
Cell Death Dis. 2023 Oct 4;14(10):648. doi: 10.1038/s41419-023-06154-8.
Autophagy is the process by which cells degrade and recycle proteins and organelles to maintain intracellular homeostasis. Generally, autophagy plays a protective role in cells, but disruption of autophagy mechanisms or excessive autophagic flux usually leads to cell death. Despite recent progress in the study of the regulation and underlying molecular mechanisms of autophagy, numerous questions remain to be answered. How does autophagy regulate cell death? What are the fine-tuned regulatory mechanisms underlying autophagy-dependent cell death (ADCD) and autophagy-mediated cell death (AMCD)? In this article, we highlight the different roles of autophagy in cell death and discuss six of the main autophagy-related cell death modalities, with a focus on the metabolic changes caused by excessive endoplasmic reticulum-phagy (ER-phagy)-induced cell death and the role of mitophagy in autophagy-mediated ferroptosis. Finally, we discuss autophagy enhancement in the treatment of diseases and offer a new perspective based on the use of autophagy for different functional conversions (including the conversion of autophagy and that of different autophagy-mediated cell death modalities) for the clinical treatment of tumors.
自噬是细胞降解和回收蛋白质和细胞器以维持细胞内平衡的过程。一般来说,自噬在细胞中起着保护作用,但自噬机制的破坏或过度的自噬通量通常会导致细胞死亡。尽管最近在自噬的调控和潜在分子机制的研究方面取得了进展,但仍有许多问题需要解答。自噬如何调节细胞死亡?自噬依赖性细胞死亡(ADCD)和自噬介导的细胞死亡(AMCD)的精细调控机制是什么?本文强调了自噬在细胞死亡中的不同作用,并讨论了六种主要的与自噬相关的细胞死亡方式,重点关注过度内质网自噬(ER-phagy)诱导的细胞死亡引起的代谢变化,以及线粒体自噬在自噬介导的铁死亡中的作用。最后,我们讨论了自噬增强在疾病治疗中的应用,并基于自噬的不同功能转换(包括自噬和不同的自噬介导的细胞死亡方式的转换)为肿瘤的临床治疗提供了新的视角。